Bottom Line:
Biokinetic studies of zinc oxide (ZnO) nanoparticles involve systematic and quantitative analyses of absorption, distribution, metabolism, and excretion in plasma and tissues of whole animals after exposure.A full understanding of the biokinetics provides basic information about nanoparticle entry into systemic circulation, target organs of accumulation and toxicity, and elimination time, which is important for predicting the long-term toxic potential of nanoparticles.This review focuses on physicochemical factors affecting the biokinetics of ZnO nanoparticles, in concert with understanding bioavailable fates and their interaction with proteins.

ABSTRACTBiokinetic studies of zinc oxide (ZnO) nanoparticles involve systematic and quantitative analyses of absorption, distribution, metabolism, and excretion in plasma and tissues of whole animals after exposure. A full understanding of the biokinetics provides basic information about nanoparticle entry into systemic circulation, target organs of accumulation and toxicity, and elimination time, which is important for predicting the long-term toxic potential of nanoparticles. Biokinetic behaviors can be dependent on physicochemical properties, dissolution property in biological fluids, and nanoparticle-protein interaction. Moreover, the determination of biological fates of ZnO nanoparticles in the systemic circulation and tissues is critical in interpreting biokinetic behaviors and predicting toxicity potential as well as mechanism. This review focuses on physicochemical factors affecting the biokinetics of ZnO nanoparticles, in concert with understanding bioavailable fates and their interaction with proteins.

Mentions:
Tissue-distribution patterns are highly dependent on exposure route, animals, and the physicochemical properties of nanoparticles. Orally administered ZnO nanoparticles of 20 and 70 nm capped with citrate/HEPES or L-serine/HEPES were determined to accumulate in kidneys, liver, and lungs in rats after a single-dose administration, regardless of particle size, surface charge, or sex (Table 1 and Figure 2).25,26 Tissue-distribution kinetics demonstrated a similar tendency to that found in plasma concentration–time profile (Figure 1), showing elevated zinc concentrations at 6–24 hours and 1–2 days in kidneys and liver after administration of 300 and 2,000 mg/kg, but returned to normal levels at 2 and 7 days, respectively. High retention of ZnO nanoparticles in lungs for the first hour can be explained by the fact that particles of 30–80 nm tend to be generally sequestered in lung tissue.31 The same target organs for ZnO nanoparticles were determined by applying optical imaging of Cy5.5-conjugation and positron emission tomography imaging of fluorinated particles.32,33 ZnO nanoparticles of 40 nm distributed to the liver and kidneys following repeated oral administration to rats for 13 weeks; however, lung distribution was not included in this study.21 On the other hand, elevated zinc levels were detected in the liver, spleen, and kidneys in mice orally administered ZnO nanoparticles of about 93 nm, and caused acute liver toxicity.34 Different tissue-distribution patterns between oral ZnO nanoparticles and ZnCl2 were demonstrated, showing higher distribution of ZnO nanoparticles in lungs, but lower distribution in kidneys and liver than ZnCl.26

Mentions:
Tissue-distribution patterns are highly dependent on exposure route, animals, and the physicochemical properties of nanoparticles. Orally administered ZnO nanoparticles of 20 and 70 nm capped with citrate/HEPES or L-serine/HEPES were determined to accumulate in kidneys, liver, and lungs in rats after a single-dose administration, regardless of particle size, surface charge, or sex (Table 1 and Figure 2).25,26 Tissue-distribution kinetics demonstrated a similar tendency to that found in plasma concentration–time profile (Figure 1), showing elevated zinc concentrations at 6–24 hours and 1–2 days in kidneys and liver after administration of 300 and 2,000 mg/kg, but returned to normal levels at 2 and 7 days, respectively. High retention of ZnO nanoparticles in lungs for the first hour can be explained by the fact that particles of 30–80 nm tend to be generally sequestered in lung tissue.31 The same target organs for ZnO nanoparticles were determined by applying optical imaging of Cy5.5-conjugation and positron emission tomography imaging of fluorinated particles.32,33 ZnO nanoparticles of 40 nm distributed to the liver and kidneys following repeated oral administration to rats for 13 weeks; however, lung distribution was not included in this study.21 On the other hand, elevated zinc levels were detected in the liver, spleen, and kidneys in mice orally administered ZnO nanoparticles of about 93 nm, and caused acute liver toxicity.34 Different tissue-distribution patterns between oral ZnO nanoparticles and ZnCl2 were demonstrated, showing higher distribution of ZnO nanoparticles in lungs, but lower distribution in kidneys and liver than ZnCl.26

Bottom Line:
Biokinetic studies of zinc oxide (ZnO) nanoparticles involve systematic and quantitative analyses of absorption, distribution, metabolism, and excretion in plasma and tissues of whole animals after exposure.A full understanding of the biokinetics provides basic information about nanoparticle entry into systemic circulation, target organs of accumulation and toxicity, and elimination time, which is important for predicting the long-term toxic potential of nanoparticles.This review focuses on physicochemical factors affecting the biokinetics of ZnO nanoparticles, in concert with understanding bioavailable fates and their interaction with proteins.

ABSTRACTBiokinetic studies of zinc oxide (ZnO) nanoparticles involve systematic and quantitative analyses of absorption, distribution, metabolism, and excretion in plasma and tissues of whole animals after exposure. A full understanding of the biokinetics provides basic information about nanoparticle entry into systemic circulation, target organs of accumulation and toxicity, and elimination time, which is important for predicting the long-term toxic potential of nanoparticles. Biokinetic behaviors can be dependent on physicochemical properties, dissolution property in biological fluids, and nanoparticle-protein interaction. Moreover, the determination of biological fates of ZnO nanoparticles in the systemic circulation and tissues is critical in interpreting biokinetic behaviors and predicting toxicity potential as well as mechanism. This review focuses on physicochemical factors affecting the biokinetics of ZnO nanoparticles, in concert with understanding bioavailable fates and their interaction with proteins.